Cancer immunotherapy emerged as a novel therapeutic option that employs enhanced or amended native immune system to create a robust response against malignant cells. The systemic therapies with immune-stimulating cytokines have resulted in substantial dose-limiting toxicities. Targeted cytokine immunotherapy is being explored to overcome the heterogeneity of malignant cells and tumor cell defense with a remarkable reduction of systemic side effects. Cell-based strategies, such as dendritic cells (DCs), fibroblasts or mesenchymal stem cells (MSCs) seek to minimize the numerous toxic side effects of systemic administration of cytokines for extended periods of time. The usual toxicities comprised of a vascular leak, hypotension, and respiratory insufficiency. Natural and strong tropism of MSCs toward malignant cells made them an ideal systemic delivery vehicle to direct the proposed therapeutic genes to the vicinity of a tumor where their expression could evoke an immune reaction against the tumor. Compared with other methods, the delivery of cytokines via engineered MSCs is safer and renders a more practical, and promising strategy. Large numbers of genes code for cytokines have been utilized to reengineer MSCs as therapeutic cells. This review highlights the recent findings on the cytokine gene therapy for human malignancies by focusing on MSCs application in cancer immunotherapy.

中文翻译：

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基因工程间充质干细胞：靶向递送免疫调节剂以根除肿瘤。

癌症免疫疗法作为一种新的治疗选择出现，它采用增强或修正的天然免疫系统来对恶性细胞产生强大的反应。使用免疫刺激细胞因子的全身治疗导致了大量的剂量限制性毒性。正在探索靶向细胞因子免疫疗法，以克服恶性细胞和肿瘤细胞防御的异质性，显着减少全身副作用。基于细胞的策略，例如树突状细胞 (DC)、成纤维细胞或间充质干细胞 (MSC)，试图将长期全身给予细胞因子的众多毒副作用降到最低。通常的毒性包括血管渗漏、低血压和呼吸功能不全。MSCs 对恶性细胞的天然和强烈的趋向性使它们成为理想的全身性递送载体，将拟议的治疗基因引导到肿瘤附近，在那里它们的表达可以引起针对肿瘤的免疫反应。与其他方法相比，通过工程化 MSCs 传递细胞因子更安全，是一种更实用、更有前景的策略。大量编码细胞因子的基因已被用于将 MSC 重新设计为治疗细胞。本综述重点关注 MSC 在癌症免疫治疗中的应用，重点介绍了人类恶性肿瘤细胞因子基因治疗的最新发现。通过工程化的 MSCs 传递细胞因子更安全，并且提供了一种更实用、更有前景的策略。大量编码细胞因子的基因已被用于将 MSC 重新设计为治疗细胞。本综述重点关注 MSC 在癌症免疫治疗中的应用，重点介绍了人类恶性肿瘤细胞因子基因治疗的最新发现。通过工程化的 MSCs 传递细胞因子更安全，并且提供了一种更实用、更有前景的策略。大量编码细胞因子的基因已被用于将 MSC 重新设计为治疗细胞。本综述重点关注 MSC 在癌症免疫治疗中的应用，重点介绍了人类恶性肿瘤细胞因子基因治疗的最新发现。